Jun
04
2016

Genetic Screening For Better Health

Dr. Matt Pratt-Hyatt gave an overview about genetic screening for better health at the 23rd Annual World Congress on Anti-Aging Medicine on Dec. 13, 2015 in Las Vegas. The title of the talk was: ”Genetic Screening: A Tool for Better Health with Age”. He showed that with more sensitive genetic screening techniques minor genetic changes can be detected. These are a lot more common than previously thought of. Matt Pratt-Hyatt, PhD is Associate Laboratory Director for the Great Plains Laboratory in Lenexa, KS.

Specifically, Dr. Pratt-Hyatt explained that single nucleotide polymorphisms, frequently called SNPs (pronounced “snips”) were the most common type of genetic variations among people. These genetic changes in the DNA often cause disease. Different types of genetic testing can identify the gene defects of SNPs. One of the questions is how aging can be better managed when genetic defects are known.

When it comes to our genetic material there are over 3 billion base pairs, all contained in 23 chromosomes. These are home to 20,000-25,000 genes, most of which are normal.

A gene has three regions all of which can have mutations. In the middle there is the coding region; one end is the regulatory region for transcription initiating; at the other end the transcription termination signals are located. Minor mutations in any of these regions can have major implications for the health of the individual or they can stay silent SNPs. SNPs are classified into missense mutation or nonsense mutation. This description just shows how intricate and complex the process of mutations can be!

There are three types of sequencing that are common:

Three types of genetic screening for better health

  1. Sanger sequencing
 utilizes certain dyes that correspond to specific nucleotides of the DNA. The benefits of Sanger sequencing is that it can cover one gene completely. It can find previously unknown mutations. But the disadvantage of Sanger sequencing is that you cannot process a large number of genes.
  2. The Florophore-base detection looks at multiple SNPs in a single run. This method is cheaper than whole genome sequencing. But one of the disadvantages of Florophore-base detection
is that only a limited number of SNPs can be processed per run. It also can miss new mutations.
  3. Benefits of next generation sequencing 
are that it can look at 1000s of SNPs per run. It is much more accurate than previous technologies. A drawback
though is that the equipment is much more expensive.

The physician does not have to order all of these tests, but can make the choice of the appropriate one for the patient. The following are some applications with regard to how genetic screening can be useful for better health.

Detoxification as part of genetic screening for better health

Since the 1970’s and 1980’s it has become clear that there are many steps in the detoxification process in the liver. It involves major enzyme systems that are controlled by the P450 genes. We know several genetic defects that run in different families. These effects are very important for drug detoxification and metabolism.

The P450 detoxification system in the liver

Any mutation in one of the P450 controlling genes will lead to accumulation of the drug that is normally detoxified by this enzyme system. Without discontinuing or lowering the drug there can be toxicity at higher levels. When people age, they often have spontaneous mutations of the P450 detoxification system. The physician who prescribes medications should take this into account. Common drugs that cause problems with the P450 controlled detoxification are antidepressants, the blood thinner Coumadin, the antibiotic erythromycin, the asthma medication Theophylline and many others.

Patient with atrial fibrillation

Here is an example of how important this knowledge is in an elderly patient who was sent to the hospital with an irregular heartbeat. The electrocardiogram allowed a diagnosis of atrial fibrillation. The doctor treated the patient with a cautious loading dose of 0.5 mg of Coumadin in an attempt to thin the blood of the patient. This would prevent a blood clot or a stroke due to the arrhythmia. Normally a small dose like this would not do much in terms of blood thinning. It would take several days of small doses of Coumadin dose like this to achieve blood thinning.

Defect of gene controlling P450 system

Unbeknown to the physician, this patient was different as he had a defect in the Cyp2c9 gene, a subtype of the P450 system. Very quickly the patient developed bleeding gums and bruising of the skin in various locations. When blood tests were taken, the INR, a measure of the clotting system, was 3.7, a value that should not have exceeded a level of 2 to 3. Genetic testing confirmed a homogenous mutation of the Cyp2c9 gene that explained the toxicity of Coumadin in this case, one of the many drugs that is detoxified by the P450 system.

Mental health as part of genetic screening for better health

Many mental illnesses can be caused by defects in various parts of the brain metabolism. This is particularly so when it involves the synthesis of brain hormones. If there are genetic defects, this can lead to the particular brain metabolism that is associated with depression or schizophrenia. Even dementia, Alzheimer’s disease and Parkinson’s disease can be caused by genetic defects. Methylation pathway defects are another source of possible genetic defects, which can affect multiple metabolic pathways. This is the cause of many diverse conditions like autism, diabetes and some hereditary cancers. The reason it is important to be aware of such genetic aberrations is that often vitamin B2, B6, niacin, vitamin B12 and the minerals magnesium and zinc can stabilize a person with methylation defects.

Cholesterol as part of genetic screening for better health

People with obesity have problems with their lipid metabolism, diabetes, high blood pressure and often heart disease and strokes. Changes in cholesterol metabolism are at the center of these problems. Cholesterol is one of the building blocks of cell membranes, and cholesterol is one of the normal components in the blood as long as the subfractions are properly balanced (LDL and the HDL cholesterol). Unfortunately many people have minor or major defects of the biosynthetic pathway of cholesterol. There are 5 genes that control the acetyl CoA biosynthesis. 21 genes involve the main cholesterol biosynthesis pathways. Over 10 genes control cholesterol metabolites. Historically these genes were detected because of various familiar gene defects that caused problems with the biochemical processes surrounding cholesterol. Familial high cholesterol levels (familial hypercholesterolemia) is one of these common conditions.

Patients who have this condition will often have high cholesterol and also often have a family history of gall bladder surgery for gallstones and a history of premature heart attacks or strokes. Early diagnosis and careful clinical intervention can improve the outlook for many patients.

Genetic Screening For Better Health

Genetic Screening For Better Health

Conclusion

Modern medicine cannot help all of the genetic conditions. But you can work around many minor genetic abnormalities. In addition, if the physician knows the genetic defect, it is possible to avoid drug interactions. It is encouraging that newer test methods have now shown success, as they are more affordable than in the past. As time progresses the price of these genetic tests will come down even further. Mental health, detoxification pathways and the metabolic syndrome of obesity are practical applications where genetic tests have significance.

Apr
23
2016

Healing Powers Of Green Tea

Powerful catechins that are a special form of bioflavonoids provide the healing powers of green tea. Researchers have proven that these catechins are only in green tea, not so much in black tea. The most effective of several catechins contained in green tea is EGCG, which stands for EpiGalloCatechin-3-Gallate. It crosses the blood/brain barrier and is very important for the protection of the brain from Alzheimer’s disease. But green tea or green tea extract has a diversified pharmacological action. Researchers said that green tea protects you from cardiovascular disease, from obesity, from diabetes, from autoimmune disorders, from cancer, from Alzheimer’s and dementia.

In the following I like to comment on how green tea or its extract can protect from all of these diseases.

Alzheimer’s disease

Although there are 5 or 6 approved anti-Alzheimer’s drugs, none of them work for very long. They may at best postpone the deteriorating memory for 6 months, but then the effect of the drug wears off. The reason is that the drugs do not stop the production of the deadly beta-amyloid. It is the beta-amyloid that damages nerve cells that you want to preserve so you can think and memorize. In contrast a simple phytochemical, the catechin EGCG has been shown in animal experiments and in human trials to stop beta-amyloid production and increase solubility of beta-amyloid fragments in the brain. The end result is better memory and no further deterioration.

Two studies showing less strokes and better working memory processing with green tea

In a study of 13,988 elderly Japanese observed over 3 years the group that consumed 3 to 4 cups of green tea daily had 33% less strokes, cognitive impairment and osteoporosis.

Researchers at the University of Basel, Switzerland enrolled 12 healthy volunteers aged 21 to 28 and fed them extracts of green tea or placebo fluid via feeding tubes. They did this to rule out taste as a factor. The patients underwent functional MRI scans and they also received memory-stimulating tasks. Only the green tea extract was boosting activity in the frontal brain of the subjects. This was located in a specific area, called dorsolateral prefrontal cortex. This area has a connection with language comprehension, reasoning and learning. It also switches short-term memory into long-term memory, called working memory processing.

Healing powers of green tea through new nerve cell development

Researchers showed with animal experiments that green tea extract protects nerve cells from the toxic effect of beta-amyloid. At the same time green tea extract triggers the production of new brain nerve cells (neurons). This is really good news for Alzheimer’s disease patients and their families: green tea extract delays further memory deterioration and stimulates the development of new nerve cells in the brain!

Cardiovascular disease

In a 2006 Japanese study 40,530 Japanese adults aged 40 to 79 years without history of stroke, coronary heart disease, or cancer at baseline were observed for 7 years. Diaries were kept about how many cups of green tea each person was drinking per day. The prevention of heart attacks and strokes was the the biggest effect of green tea extracts.

Men had a mortality reduction of 12% for heart attacks when they drank 5 cups or more of green tea; in women the corresponding mortality reduction for heart attack was 31%, a bigger effect. Overall mortality from strokes was lower than from heart attacks. This made the effect of green tea consumption even more beneficial with respect to stroke prevention. This study did not show any cancer prevention effect for green tea.

Obesity

It appears that green tea increases heat production and burns fat in the process. There was a small effect in terms of weight loss and a beneficial effect increasing the protective HDL cholesterol in this 2012 Polish study on obese patients. The authors compared either 379 mg of green tea extract, or a placebo, daily for 3 months. They concluded: “The results of this study confirm the beneficial effects of green tea extract supplementation on body mass index, lipid profile, and total antioxidant status in patients with obesity.”

Diabetes

Although there are claims in some studies that green tea would prevent diabetes, this question was thoroughly investigated in this Chinese 2014 study.

Researchers did not see any effects on fasting blood sugars or on hemoglobin A1C values. Hemoglobin A1C is a very sensitive indicator for the presence or absence of diabetes. All these lab tests showed no change following consumption of green tea or green tea extract. Forget using green tea for diabetes prevention; cut out sugar and starchy foods instead.

Autoimmune disorders

Sjogren’s syndrome and lupus are both autoimmune diseases. Green tea extract has shown in humans that symptom severity can improve; green tea polyphenols (GTPs) possess anti-inflammatory properties that benefit patients with autoimmune diseases.

In an animal model arthritis researchers determined that T helper cells are weakened and bone resorption is inhibited by EGCG from green tea extract.

Researchers at Harvard Medical School, Boston, MA have noted that green tea extract is useful in calming down the immune response in autoimmune diseases. They concluded: “Altogether, these studies identify and support the use of EGCG as a potential therapeutic agent in preventing and ameliorating T cell-mediated autoimmune diseases.”

Cancer

Many researchers found that EGCG from green tea extract has immune modulatory effects. Furthermore, they saw a positive effect when patients received EGCG in combination with chemotherapy. A combination of cisplatin therapy with green tea extract has been found to have more effects on colorectal cancer and ovarian cancer than each one on its own. Similarly chemotherapy of breast cancer had better results in humans when EGCG from green tea extract was added as an immune modulation. More research, particularly in humans is needed to fully understand the mechanism of action of EGCG.

Toxicity of green tea extract

Animal experiments showed that higher doses of green tea extract could cause toxicity in the liver and in the nose of rats and mice. I was not able to find objective evidence for green tea toxicity in the PubMed system with respect to humans.

Healing Powers Of Green Tea

Healing Powers Of Green Tea

Conclusion

Perhaps the most important discovery regarding green tea extract is as follows. It crosses easily through the blood/brain barrier into the brain. This can postpone Alzheimer’s disease and can even lead to new neuron formation. The beneficial cardiovascular effects are also useful and combine well with exercise and good nutrition for prevention. Particularly stroke prevention is a useful property of EGCG from green tea extract. The effect on obesity is marginal whereas there was no effect of green tea on prevention of diabetes. The immune modulatory effect of green tea extract is useful in the treatment of autoimmune diseases and of cancer. Existing treatments for these conditions are becoming more effective by adding green tea extract.

Apr
02
2016

Women Win Turning Older

Supercentenarians may teach us something about the question “Why do women win turning older”? Supercentenarians are people who are 110 years or older. Presently there are 53 of them distributed over the world, 51 are females and two are males. According to Ben Dulken and Anne Brunet this is not by chance: in other mammal species females often live longer than their male counterparts. They theorize that stem cells live longer under the influence of estrogen and this may be the explanation for the difference. They wanted to answer the burning question: “Is life expectancy linked to gender and stem cells”?

Observations regarding why women win turning older

Ben Dulken and Anne Brunet describe that several pieces of evidence are important to note.

Human eunuchs live longer than average males

Castrated males, called eunuchs, live on average 14 years longer than the average male.

Treatment of male mice with estrogen caused longevity

Experiments with male mice treated with estrogen increased their lifespan compared to untreated male controls.

Estrogen receptors on some stem cells in women

Neural stem cells (NSCs) and hematopoietic stem cells (HSCs) have estrogen receptors in females. This leads to extra stimuli during pregnancy, but also during the menstrual cycle in women or the estrus cycle in female mammals.

Faster wound healing in women may be from extra X-chromosome

It gets more complicated: There are non-estrogen regulated stem cell niches in the liver, skin and subcutaneous tissue (important for wound healing and resident muscle stem cells, called satellite cells (SCs). For some reason liver regeneration and wound healing, but also healing of muscle injuries in women and female mammals occurs at a faster pace. Scientists still do not have an answer for this. Theories are that perhaps women with their two X-chromosomes are at an advantage in comparison to males (only one X-chromosome) with respect to certain wound repair mechanisms.

Longevity and self-repair capacity may be related

There is the question whether longevity and self-repair capacity would be related, either through stem cell populations (NSCs, HSCs, SCs), other repair mechanisms or tissue proliferation.

Telomere length in older persons longer in females than in males

There are gender differences in aging patterns of stem cells. For instance studies in dizygotic twins showed that telomere length of blood cells in the female twin was much longer than in the male twin. Genetic factors appear to be the dominant factor to explain this phenomenon rather than hormones. But again this was favoring the female.

Comparison between muscles in older men and younger men

A study in males showed that there is an accumulation of damaged DNA in SC’s of muscle tissue with older age that leads to muscle senescence. In older men there is a delayed response to a specific exercise stimulus with regard to the satellite cell division (SC) when compared to the response in young men.

Women’s telomeres in stem cells grow longer

In females estrogen stimulates telomere growth of stem cells (NSCs and HSCs), which prevents premature stem cell exhaustion.

Effects of diet and exercise on life expectancy

The Potsdam study analyzed 4 healthy behaviors in 23,153 German participants aged 35 to 65 years over 7.8 years. They looked for the development of cancer, heart attacks, strokes and cancer as end points. The 4 healthy behaviors were: to be a lifelong non-smoker , having a body mass index lower than 30, performing 3.5 h/week or more of physical activity, and adhering to healthy dietary principles (high intake of fruits, vegetables, whole-grain bread and low meat consumption).

Those who had adopted all 4 healthy lifestyles reduced the development of serious disease by up to 80%. Dr. David Katz delivered a keynote address at the 22nd Annual World Congress on Anti-Aging Medicine in Las Vegas Dec. 10-14, 2014 entitled “Integrative Medicine: A Bridge Over Healthcare’s Troubled Waters”. He mentioned the Potsdam study. And he mentioned what the new logic of a healthy lifestyle is: a healthy lifestyle causes healthy telomeres of somatic cells and of stem cells; this causes health until a ripe old age.

Life Expectancy Linked To Gender And Stem Cells

Life Expectancy Linked To Gender And Stem Cells

Conclusion why women win turning older

It seems that women and female mammals are more protected by nature than males. The previously called ”weak sex” is in fact a lot stronger! This may be the reason that among supercentenarians there are only a few males remaining. But we don’t know how many males take the lifestyle factors of the Potsdam study serious. Males who want to age gracefully have to pay more attention to healthy lifestyles. This leads to longer telomeres and this allows for stem cell and somatic cell renewal. There are still many unanswered questions, but life expectancy is definitely related to how well we preserve stem cells throughout our body. This in turn depends very much on our lifestyle patterns.

Mar
19
2016

Book Review: “Healing Gone Wrong – Healing Done Right”, By Ray Schilling, MD

This book entitled “Healing Gone Wrong – Healing Done Right” (Amazon, March 18, 2016) is dealing with the practice of medicine then and now. Medical errors, false diagnoses and wrong treatments are nothing new in the history of medicine. It happened in the past, and it is happening now. My first book was about anti-aging. The title was “A Survivor’s Guide to Successful Aging” (Amazon 2014).

Book overview

Chapter 1

Here I describe describe that famous people like President Kennedy, Elvis Presley, Churchill, Beethoven or more recently Michael Jackson have something in common: all of them suffered the consequences of blatant medical mistakes. In Beethoven’s time lead containing salves to plug the drainage holes from removing fluid from his abdomen caused lead poisoning. In this chapter I review also how doctors treated the illnesses of the above-mentioned celebrities, but then ask the question: “What better treatments have offered to prevent some of the disastrous treatment outcomes?”

Chapter 2

Modern drugs seem to come and go. We learn that twenty-first century medications that are supposed to be the latest therapeutic agents are having their potentially deadly consequences too: COX-2 inhibitors, the second generation arthritis drugs cause strokes and heart attacks! Your doctor may still prescribe some of these dangerous drugs for arthritis now.

Chapter 3

This chapter deals with the fact that medical treatments for people’s diseases may be inappropriate when the doctor treats only symptoms, but the doctor does nothing about the causes of their illnesses. This is a scary thought.

Chapter 4

What does it take to prevent these poor health outcomes, so that we will be able to prevent any disastrous outcomes pertaining to our own health care in the present and future? As we will see, the problem today is still the same as it was in the past, namely that many physicians still like to treat symptoms instead of the underlying cause of an illness. Big Pharma has the seducing concept of a pill for every ill, but it is not always in your best interest, when these medications have a slew of side effects. “Gastric reflux” means a mouthful of stomach acid. Big Pharma simply offers the patient with the symptom of gastric reflux a multitude of medications to suppress this symptom. But it is more important to dig deeper to find the reason for the illness and treat the underlying cause.

Chapter 5

We all need our brain to function. This chapter concentrates on the brain and how we can keep our brains functioning optimally until a ripe old age. This review spans from prevention of head concussions to avoiding type 3 diabetes (insulin sensitivity from overconsumption of sugar). It manifests itself in Alzheimer’s disease. It is a form of diabetes of the brain that leads to deposits of a gooey substance. Prevention of this condition is also reviewed .

Chapter 6

This chapter reviews what we now know about how to keep a healthy heart. Certain ingredients are necessary such as regular exercise, a healthy Mediterranean diet, supplements etc. The good part is that what is good for the heart is also good for the brain. You are preventing two problems (brain and heart disease) at the same time.

Chapter 7

What should we eat? And why does healthy food intake matter? Without the right ingredients of our body fuel, the body machinery will not work properly. The Mediterranean diet is an anti-inflammatory diet that is particularly useful.

Chapter 8

We need healthy limbs, bones and joints. We are meant to stay active in our eighties and nineties and beyond. No osteoporosis, no joint replacements, no balance problems that result in falls! Learn about how to deal with problems like these in this chapter.

Chapter 9

This chapter deals with detoxification. What do we do as we are confronted with pollution, with radiation in the environment and poisons in our daily food? A combination of organic foods, intravenous chelation treatments and taking supplements can help us in that regard.

Chapter 10

I am dealing here about reducing the impact of cancer in our lives. A lot of facts have come out in the past 10 years telling us that reduction of sugar and starchy food intake reduces cancer. Curcumin, resveratrol and vitamin D3 supplements also reduce cancer rates as does exercise and stress management. All of this is reviewed here.

Chapter 11

This chapter tells you all you need to know about your hormone status. Women need to avoid estrogen dominance; both sexes need to replace the hormones that are missing. By paying attention to your hormonal status and replacing the missing natural hormones with bioidentical ones, most people can add 10 to 15 years of useful, active life!

Chapter 12

Here you will learn more about anti-aging. You will learn about the importance to keep your mitochondrial DNA healthy. Apart from that there are ways how to keep your telomeres longer; certain supplements that are reviewed will help. Also your lifestyle does make a big difference in how old you can turn.

Chapter 13

This chapter investigates the limits of supplements. Many supplements are useful, but you do not want to overdo it and get into toxic levels. More is not necessarily better!

Chapter 14

Here is a review of an alternative approach to treating ADHD. Attention deficit and hyperactivity disorder has been over diagnosed, has been neglected and has been over treated with dangerous drugs. An alternative treatment plan is discussed, which includes a combination of therapeutic steps.

Chapter 15

This gives you a brief summary of the book.

Kirkus Review

Kirkus Reviews reviewed the book on March 17, 2016: “A retired physician details how various preventative measures can fend off disease and disability in this consumer health guide. Schilling (A Survivor’s Guide to Successful Aging, 2014) had a family medicine practice in Canada for many years before retiring. Although Schilling ventures into some controversial territory in his latest book, it’s generally an engaging, helpful synthesis of ideas that draws on reputable research from the Mayo Clinic and other sources. Overall, it serves as an intensely detailed wake-up call to the importance of preventative health. He largely brings an accessible and even-tempered tone to his narrative, warning readers, for example, that preventative health measures can only aid in “a delay of aging, not ‘eternal living.’ ” A thought-provoking, impassioned plea to be proactive about one’s health.”

Healing Gone Wrong – Healing Done Right

Healing Gone Wrong – Healing Done Right

Conclusion

In this book it becomes evident that it is better to prevent an illness whenever possible rather than to wait for illness to set in and cause disabilities or death. You heard this before: “Prevention is better than a cure” or “an ounce of prevention is better than a pound of cure”. I will give an explanation, based on scientific data that there is indeed evidence to support these notions on a cellular level.

Mitochondria, the energy packages within our cells

The mitochondria, the energy packages within our cells, are the driving force that keep people vibrantly healthy well into their nineties. All this can only happen when the mitochondria function properly. If toxins poison the mitochondria and as a result they malfunction, we are not looking at a person with vibrant health. Instead sixty or seventy year-olds may use a wheelchair. If you want a life without disabilities, a life without major illnesses and enjoy good health to a ripe old age, you are reading the right book.

The book is written in American English.

Available in the US: http://www.amazon.com/gp/product/1523700904

In Canada: https://www.amazon.ca/Healing-Gone-Wrong-Done-Right/dp/1523700904/  

In other countries the book is available through the local Amazon websites.

Jan
31
2016

The Gut and Brain Connection

There is a lot of talk about the gut and brain connection. At the 23rd Annual World Congress on Anti-Aging Medicine (Dec. 11-13, 2015) in Las Vegas there were several lectures pointing out the importance of the gut flora for proper brain function. As a matter of fact, if you have the wrong gut flora, you can get a number of diseases like diabetes, fibromyalgia, rheumatoid arthritis, multiple sclerosis, muscular dystrophy, some cancers and even obesity. Martin P. Gallagher, MD, DC talked about this in his talk entitled “Gut on Fire, Brain on Fire!”

Function of the microbiome

The microbiome is the sum of all microbial organisms inhabiting the human body, which colonize mainly the colon, but also to a lesser degree the small intestine. Dr. Gallagher stated that the microbiome weighs only 7.1 oz., although in the past some have estimated its weight to be as high as 3 pounds. The purpose of the microbiome is to help form a gut/blood barrier. It forms a 30-micron thick layer in the GI tract, protects the intestinal lining and metabolizes food remnants, especially from carbohydrates. In addition, it also communicates with the immune system. There is a cross talk between the lining of the gut and the and the body’s immune system. The gut bacteria help the body to create stability; as a result the good bacteria also decrease intestinal permeability.

Leaky gut syndrome develops

When inflammation occurs in the gut, the thickness of the biofilm is less than 30 microns. Intestinal permeability increases and becomes “leaky gut syndrome”. This can be the cause of autoimmune diseases and possibly other diseases.

The enteric nervous system

The gut can produce as many neurotransmitters as the brain and spinal cord can synthesize. The enteric nervous system communicates with the brain through the vagal nerve. Serotonin is an important neurotransmitter that regulates motility of the gut. The control system of the gut can work on its own and override the concerns of the central nervous system.

Parkinson’s disease is a disorder of the enteric nervous system as well as the brain. With Alzheimer’s disease the characteristic brain lesions are also present in the enteric nervous system!

A mouse experiment showed the following. The Lactobacillus strain is  normally part of the microbiome of the gut.  Re-introduction of Lactobacillus into the gut flora resulted in healing certain parts of the brains of these animals, which researchers associate with anxiety and depression. But when the researchers severed the vagal nerve of these animals, none of these healing changes occurred.

The gut-brain-axis

For this reason the researchers suggested that the gut bacteria are able to communicate with the brain via the vagal nerve. Researchers have coined this connection the “gut-brain axis”. These protective gut bacteria have the ability to protect humans from gastric acidity, from bile acid toxicity, they adhere to the lining of the gut and they persist to reside within the gastrointestinal tract. Probiotics help the immune system to maintain the immunologic memory and to secrete antibodies, called immunoglobulins.

Two strains with benefit to humans are Lactobacillus rhamnosus GG and Saccharomyces boulardii. Probiotics often help against diarrhea. The natural food for gut bacteria in the colon comes from starches of chicory, asparagus, inulin and onions that are indigestible in the stomach and small intestine, but are fermented in the colon to provide food for the bacteria residing there.

Small Intestinal Bacterial Overgrowth (SIBO)

Overgrowth of the small intestine with bacteria that produce endotoxins appears to have significance in both animal models and human disease. Chlamydia species as well as Borrelia burgdorferi (Lyme) can produce toxins that cause hypersensitivity to pain in soft tissues in fibromyalgia and animal models of fibromyalgia. Moreover, SIBO – small intestinal bacterial overgrowth – in experimental animals caused the same hypersensitivity of the soft tissues and also leaky gut syndrome.

Risk factors for SIBO

What causes SIBO is too little stomach acid production, treatment with proton pump inhibitors (powerful anti acid medications) and antibiotics. To summarize, Dr.Gallagher said that SIBO also occurs in post-surgical patients, in patients with diabetes, is brought on by alcohol, nicotine, drugs and GMO foods.

Neurogenic inflammation

Normally the blood brain barrier keeps immune cells from the body out of the brain. Only glucose, proteins and lipids are allowed into the brain, but not lipophilic neurotoxins. In contrast, neurogenic triggers, when admitted to the brain, will compromise the function of the immune cells of the CNS, called microglia. In essence, this can result in memory loss, Alzheimer’s, dementia, seizures, migraines, Parkinson’s Disease, multiple sclerosis, cancer, weakness, numbness, etc.

What triggers inflammation?

Here is a long list of different items that cause inflammation: aging, hormone deficiencies, obesity, diabetes mellitus, cardiovascular disease, fungal infection, the Standard American diet (SAD), pain, trauma and mechanical stress, heavy metals, food allergies, toxins, gut dysbiosis, small intestinal bacterial overgrowth, mal-digestion/absorption, prescription drugs, over-the-counter drugs, recreational drugs and alcohol, lack of exercise and lack of sleep.

Neurotoxic insults start the chain of reactions  like heavy metals, nutritional deficiencies, viruses/fungus/bacteria, inflammatory diet, MSG, solvents, pesticides, herbicides, etc.. One or more of these factors destabilize the tight junctions of the blood brain barrier, which leads to neurogenic inflammation.

Result of neurogenic inflammation

The result is Parkinson’s disease, MS, dementia, chronic pain, behavioral and personality changes, Alzheimer’s disease, ALS and Lyme disease. What seems to be happening a lot is that there is overgrowth of abnormal bacteria in the small bowel, which produce toxins. These in turn lead to leaky gut syndrome, which allows neurogenic triggers to attack the blood brain barrier. It seems like from here it is a short step to neurotoxic insults of the brain overstimulating the microglia, which will produce the diseases listed above.

Healing of brain inflammation

First of all, treatment starts with the Mediterranean diet, which has been shown to have anti-inflammatory properties. Second, people who are gluten sensitive need to eliminate gluten entirely from their food. Third, casein sensitive people need to eliminate dairy products. Furthermore, a triple strength, molecularly distilled fish oil product is taken as a supplement every day with 4 grams or more of DHA/EPA. This helps the anti-inflammatory response.

Glutathione

One of the most powerful antioxidants and anti-inflammatories is intravenous glutathione. This is given as intravenous chelation therapy, which removes heavy metals. Other chelation agents such as EDTA intravenously may be given alternatively. Dr.Gallagher said that glutathione serves as primary cellular defense against free radicals, is a powerful antioxidant and serves as detoxifying agent against xenobiotics. Xenobiotics are remnants of artificial fertilizers, pesticides and pollutants that are contained in crops we eat.

Dr. Gallagher gives 600mg of glutathione twice per day intravenously for 30 days. Uniquely, in Parkinson’s disease patients whose mid brain is often poisoned by mercury this leads to 42% decline of disabilities and the effect lasts for 2 to 4 months after this treatment has been stopped. Coupled with this the treatment also protects telomeres, the caps on the ends of cellular DNA as well as mitochondrial DNA. In addition, glutathione is protective of neurons and nerves.

Curcumin

This common Indian spice, found in turmeric is a potent anti-inflammatory. It is a safe natural agent and has also anti-viral and anti-tumor activities. It binds to the vitamin D receptor and works synergistically together with vitamin D3. Solid lipid curcumin particle technology makes curcumin 65-fold more bioavailable; free curcumin is allowed to pass the blood brain barrier. Lower doses achieve the same effect than regular curcumin.

According to a publication using lipidated curcumin the following observations were made: improved vascular function; equally important, inflammatory markers reduced by 14%; in like manner, triglycerides lowered by 14%; by the same token, oxidative stress reduced; not to mention, catalase increased and finally total antioxidant status improved. Here is another paper about lipidated curcumin.

Omega-3 fatty acids

Omega-3 fatty acids are anti-inflammatory by countering the arachidonic acid pathway that leads to inflammation. Physicians recommend it as triple strength, molecularly distilled fish oil. DHA/EPA are the active ingredients. Chronic inflammation requires 2 to 12 grams daily; irritable bowel syndrome 6 to 12 grams daily; depression, anxiety and insomnia require 2 to 4 grams per day; autoimmune disease, back pain and degenerative joint disease 4 to 12 grams per day.

Gut/brain dysbiosis

For gut/brain dysbiosis Dr. Gallagher recommended to start with a 10-day fruit/vegetable detox program. Milk thistle, glutathione and pancreatic enzymes in combination lead to improvement. Lipidated curcumin is also useful. The physician also gives glutamine, prebiotics and probiotics for gut support. He also tells the patient to take molecularly distilled fish oil (DHA/EPA) and vitamin D3 as anti-inflammatories. Doctors also administer oral and intravenous glutathione to detoxify. Many doctors use natural as a combination of glutathione, oregano, olive leaf and silver salts.

The Gut and Brain Connection

The Gut and Brain Connection

Conclusion

Inflammation can start in the gut, lead to leaky gut syndrome and break down the blood/brain barrier. The end result is that inflammation develops in the brain and Alzheimer’s disease and dementia can occur. The sooner the physician starts with treatment, the faster the recovery is. When the patient has reached the end stage, it is difficult to turn the inflammatory process around. Fortunately there are effective ways to get the inflammation under control with intravenous glutathione in the beginning and subsequent treatment with lipidated curcumin, omega-3 fatty acid and vitamin D3. A permanent switch to a Mediterranean diet is important as well to keep inflammation under control.

Lifestyle and nutrition choices are important for prevention

A few years back this mainstream medicine considered this type of approach as “quackery”; now it is the latest information from research into the brain/gut connection. The right lifestyle and nutrition choices can do a lot on a preventative basis. Once disease has taken root, treatment may still be possible, but once it is at a later stage a full cure is unlikely.

Incoming search terms:

Jan
23
2016

Life Extended By Several Decades

Have you ever thought about the possibility to prolong your “Freshness Date”? At the 23rd Annual World Congress on Anti-Aging Medicine on Dec. 13, 2015 in Las Vegas the endocrinologist, Dr. Thierry Hertoghe from Belgium gave a talk about “How to extend the human lifespan by 40 years”. Dr. Hertoghe explained that it is possible to extend life by paying attention to the factors that prolong life and combining them as an anti-aging type lifestyle. He made a distinction between

  1. normal aging: up to age 82
  2. healthy aging: up to age 100
  3. anti-aging medicine: up to age 122
  4. reversing aging medicine: much more than 122, perhaps to age 150 or more.

Normal aging (up to age 82)

Life expectancy is on average about 82 years. From the age of 50 to 60 onwards you may encounter problems with increased cholesterol, high blood pressure leading to heart attacks and strokes. Coronary artery by-pass surgery may extend an individual’s life by 10 to 15 years. But hardening of the arteries in the general circulation will eventually cut down the blood supply to vital organs leading to premature death that could have been avoided.

Around the mid 60’s to mid 70’s 12.4% of African Americans or 2.9% Caucasians get Alzheimer’s disease. These figures worsen rapidly with further aging: in their mid 70’s to mid 80’s 32.5 % of African Americans and 9.8% of Caucasians suffer from Alzheimer’s disease. At the age of 85+ years 54% of African Americans and 27% of Caucasians have Alzheimer’s disease. With normal aging Alzheimer’s has already increased, and this trend likely is continuing.

Loss of memory, depression and musculoskeletal pain

Memory loss also leads to a shortened survival curve; people with memory loss live two years less on average than compared to a group with no memory loss.

Add to this loss of life because of depression, common in older age. Compared to a non-depressed group over 2 years of older people the depressed group lived 30% shorter.

Musculoskeletal pain in younger age (18-44) was 38%; the next demographic group aged 45-64 reported 61% of musculoskeletal pains; seniors between 65 and 74 had 68% of musculoskeletal pain, and in the demographic group of 75 and up 71% of persons suffered of musculoskeletal pain. As we will learn later there may be hormone deficiencies behind these neck and back pains. If the patient does not seek treatment, this can lead to falls, fractured hips and premature loss of life. Those who survive accidents often become wheel chair bound and end up in nursing homes.

Patients with rheumatoid arthritis and patients with other disabilities have a lower life expectancy

One specific subgroup of patients with musculoskeletal pain are rheumatoid arthritis sufferers. After 10 years of having rheumatoid arthritis patients will have a survival of only about 50%. With involvement of more than 30 joints  (more severe form of the disease) only about 40% will survive. In other words, rheumatoid arthritis is an important factor for lowering people’s life expectancy.

At an age of 65 to 74 men have 23% of disabilities, while woman have 27.5% disabilities. This increases between the ages of 75 or older to 40% for men and 44.5% for women. At the age of 65 disabled men have a 3.5% higher death rate than the average population; disabled women’s death rate is 2.5% higher than the normal population. In other words, disability kills.

Obesity, and heart disease

Urinary urgency and incontinence leads to a 3.13-fold higher mortality rate than a control group of men who do not have these symptoms.

65% of men and 85% of women above the age of 50 have abdominal obesity. This is not just a harmless condition. There is an association between increased triglyceride levels and increased mortality due to cardiovascular disease and diabetes.

By the age of 65-74 heart disease has a frequency of 32% in men and 23% in women. At the age of 75 years and older this jumps to 44% in men and 32% in women. Once the doctor diagnoses heart disease, it causes a lot of premature deaths: an average person with heart disease lives 10 years shorter than those who do not have heart disease!

Healthy aging (up to age 100)

Improving lifestyle factors increases life expectancy

If we look at normal aging, we realize that all these diseases and disabilities we discussed are eventually killing us. In order to live longer we have to take steps that are known to interfere with some of these factors. For instance, quitting smoking will prevent heart disease, several cancers and chronic obstructive lung disease (emphysema). Positive thinking, social support and transcendental meditation will increase survival by preventing mental illness and depression, which in turn will prevent suicides. A healthy diet such as the Mediterranean diet or the Pegan diet will avoid cardiovascular disease and cut down cancer rates.

Live longer with better diet

One dietary change is called the “polymeal”. It consists of fish, fruit, vegetables, garlic, almonds, a moderate amount of wine and dark chocolate. Compared to the Standard American diet this type of diet would add 9 years for men and 8.1 years for women regarding their life expectancy. For instance, prostate cancer showed a 7-fold increase in a group of men who ate a lot of pickled vegetables, fermented soy products, salted fish and preserved meats, when compared to a control group who did not include these foods. In a group of women who had their meat well done and ate three servings of beef per week, breast cancer risk was 4.62-fold higher compared to women who ate meat done rare or medium rare. Overall cancer and cardiovascular mortality dropped by 35% in a study where 5 or more servings of fruit and vegetables were eaten per day.

Regular exercise and supplements of vitamin C and omega-3

A regular exercise program will strengthen the heart and lungs, keep your weight stable, reduce heart attacks and strokes and reduce the probability to develop cancer. A group of men between 61 and 81 were observed over 12 years and divided into those who did not exercise versus those who walked more than 2 miles per day. The exercising men had 19% less mortality compared to the sessile men. Vitamin C from fruit and vegetables or from taking supplements reduces global mortality from all causes by 46% compared to controls that did not. Similarly taking omega-3 fatty acid supplements (fish oil) daily reduced all cause mortality by 20%.

Dr. Hertoghe calls this “healthy aging” and this would allow you to be able to reach an age of about 100 years.

Anti-aging medicine (up to age 122)

Low thyroid hormones

Dr. Hertoghe told the audience that further attention to anti-aging factors could reduce mortality even further. He found over the years that paying attention to correcting hormonal weaknesses would have profound effects on how old a person becomes. Thyroid hormone replacement has been one of the steps that has helped people to feel more energetic, have less muscle pain, less falls, less fractures and complications. It also translates into longer lives.

One slide showed that a low free T3 level (low thyroid) was associated with a 3.6-fold higher death rate. A low free T3 level is an accurate predictor of cumulative death rate in cardiac patients.

T3 is also important for the maintenance of the immune system, which shows in patients with tuberculosis: the one-year mortality rate from TB in thyroid deficient patients was 75%, while patients with a normal thyroid had a mortality from TB of only 7%.

Replacement of missing sex hormones

Secondly, replacing missing sex hormones can add more life because cardiovascular disease is postponed (less heart attacks, less strokes), there is less cancer and better cancer survival, if a person comes down with cancer. Many statistics were quoted.

One interesting slide showed the longitudinal survival follow-up of congenital dwarfs in comparison with their normal brothers or sisters. Untreated male dwarfs turned only 56 years on average, while their unaffected normal brothers turned 75 years on average (19 years longer). With female dwarfs the difference is even more striking: untreated females dwarfs turned 46 years on average, while their normal sisters turned 80 years on average (a difference of 34 years).

Bioidentical hormone treatment prolongs life, lowers heart attack rates and lowers cancer rates

Another publication showed that the heart attack risk was 3.8-fold higher in a group of patients with hypopituitarism (under function of the pituitary gland), but the treatment group (treated with GH) had a normal rate of heart attacks.

11606 men aged 40 to 79 years were followed for between 6 and 10 years. The group who had the top 25% range of testosterone had a 19% lower mortality rates from heart attacks or cancer.

Older women, particularly aged 100 in Okinawa had 2.3-fold higher testosterone levels than women in the US at age 70. On the other hand 70-year old Okinawan women had 2.7-fold higher estrogen levels than US women.

Bioidentical hormone replacement therapy (BHRT) prior to developing breast cancer showed a 27% longer survival among 984 breast cancer patients in Sweden compared to those without prior hormone treatment.

Lower mortality rates for bioidentical hormone replacement therapy of breast cancer patients

In another group of breast cancer patients (2755 patients) aged 35 to 74 who were treated with bioidentical hormone replacement therapy (BHRT) after their breast cancer diagnosis, 50% had a lower recurrence rate (compared to no-BHRT treatment) and there was a reduction of 66% of mortality from breast cancer compared to controls without BHRT treatment. Another study showed that breast cancer patients would have a mortality rate of 33.3% without hormone treatment. After non-estrogen hormone treatment the mortality rate dropped to 12.5% and to 6% after estrogen/progesterone use. This shows the healing results of the various natural hormones.

Treating the cause rather than the symptoms

A group of 280 men and women around the age of 50 were treated with anti-aging hormone replacement for 2 or more years. In the beginning there were 34% of women and 15% of men with coronary artery disease. There were also 36.4% of women and 34.1% of men with high blood pressure. After replacing all of the missing hormones with bioidentical hormones for more than 2 years, coronary artery disease had dropped to 1.6% of the women and 1.08% of the men; high blood pressure had dropped to 2% of the women and 3% of the men. No drugs, just hormones! Of course, initially the doctors prescribed drugs to stabilize their condition, but they could gradually drop them safely. The reason was that the doctors treated the underlying hormone deficiency. The doctors were treating the cause of the cardiovascular disease rather than only the symptoms.

Low mortality of women on bioidentical hormone replacement

Dr. Hertoghe presented data of 6.38-year follow-up of 286 consecutive patients using anti-aging medicine (replacement of missing hormones with bioidentical hormones). These patients had an overall cancer rate of 2.1%, which compared very favorably to the 3.2% cancer rate among US women. The overall cancer rate was  3.1% in French women and 3.1% in Belgium women on no hormones. This is the type of information that is needed following the Women’s Health Initiative (WHI) that scared women into the false belief that hormones would be “poisonous”.

Synthetic hormone do not fit the hormone receptor

In the WHI synthetic hormones caused cancer and heart attacks; the reason for this was that synthetic hormones are not the identical shape as the natural hormones. But hormones and hormone receptors have to fit like a key into a lock; otherwise they are not effective or even block the natural life prolonging action of the natural hormone. This is why in the WHI study the outcomes were poor. Using bioidentical hormones the doctor can prevent heart attacks and strokes and they are also cancer-protective.

Reversing aging medicine (much more than 122, perhaps to age 150 or more)

General medicine has the goal to make patients as healthy as possible. With reversing aging medicine the goal is to make patients as young as possible. They are at their healthiest and feel younger again.

With anti-aging medicine using a healthy diet, exercise and bioidentical hormone replacement therapy the patients can add 15 years of good life. Add to these organ transplants, if necessary, telomerase activators and stem cell therapy. This can add another 25 years of life expectancy to a total of 40 years.

Growth hormone deficiency

Growth hormone deficiency is the one factor that has been underestimated. The discussion of dwarfs in comparison to their healthy brothers and sisters showed us the following. Growth hormone production can add between 19 and 34 years (average 26.5 years) of life. Dr. Hertoghe has done blood tests (IGF-1) and lately also 24-hour urine metabolite tests of growth hormone on aging patients and found that many are deficient with regard to GH production. These were patients where Dr. Hertoghe already replaced their thyroid hormones, if abnormal and replaced their sex hormones when they were low. But they lost hair, developed old looking faces with wrinkles. In addition, a loss of subcutaneous fatty tissue is giving the face a hollow appearance. They also had muscle and joint pains and thin skin, particularly over the back of their hands.

Replacement of growth hormone

He replaced their missing GH using daily GH self-injection with a tiny needle (similar to diabetes injections). Within 1.5 to 3 years the wrinkles disappeared, the faces started to look younger and patients did feel younger. Their muscle and joint pains had disappeared and their hair grew back. The dosage range is between 0.1mg and 0.3mg, a tiny amount of GH daily. This is not inexpensive, but some health care plans pay for this, as a lack of GH is a true hormone deficiency.

About organ transplants

Often it is a single limiting organ that determines when we die, typically the heart, lungs, brain, liver, kidneys, small bowel, pancreas or bone marrow. Organ transplants can add years of life, but it can be cumbersome to find a suitable donor. One study showed that only 40% to 60% of organ transplants are surviving 8 years after the surgery.

Stem cell therapies are other ways to prolong life. More research will perfect this, but essentially stem cells can provide 220 different cell types for in-vitro organ culture. This can probably be of use in the future to replace malfunctioning organs.

Life Extended By Several Decades

Life Extended By Several Decades

Conclusion

The dream of staying younger for longer can be a reality today. You just need to be willing to discipline yourself and watch what you are eating (Mediterranean type diet). Also, exercise regularly and have a positive psychological attitude. If the outdoor air is poor where you live, you may want to consider moving. Move to a place with good air quality. Sleep well for 7 ½ hours every night and retire not later than 10 to 11PM. You need to be asleep between midnight and 3AM as the growth hormone peak occurs at that time.

Take supplements

Take supplements that contain longevity micronutrients (magnesium, vitamins A, C, D, E, B6, B12, Co-Q-10, selenium, zinc, iron in premenopausal women etc.). Replace all missing hormones with bioidentical ones, like thyroid hormones (T3 and T4), sex hormones, DHEA and GH. Stem cell therapy and telomerase activators for cell rejuvenation will also have more of a place in the future.

Even, if you do only part of this reversing aging program you will slow down aging.

Dec
26
2015

Coffee Could Be A Lifesaver

Coffee could be a lifesaver. But coffee has long been a subject of heated discussions. It has been praises or condemnations. Researchers designed many studies in the past; some showed health benefits, some did not. A new, larger study was done by the Department of Nutrition, Harvard School of Public Health in Boston, MA to re-examine this issue for both caffeinated and decaffeinated coffee.

Here is the study showing why coffee could be a lifesaver

Mortality was determined among 74,890 women in the Nurses’ Health Study (NHS), 93,054 women in the NHS 2, and 40,557 men in the Health Professionals Follow-up Study after a medium follow-up of 22.5 years. 19,524 women and 12,432 men died during that time period. Ming Ding is a doctoral student in the Harvard School of Public Health department of nutrition and was the lead author of the study that was published in the medical journal “Circulation”. She pointed out that in the past there were confounding problems: although many studies had shown that both caffeinated and decaffeinated coffee consumption lowered the risk of cardiovascular disease, the results in many studies were blurred. Studies often did not distinguish between smokers and nonsmokers; so a beneficial effect from coffee drinking was wiped out by the cardiovascular risk from smoking.

Ding’s studies took this into account and also other confounding factors like how much sugary soda pop people were drinking and whether or not they were eating well. In addition they normalized for other factors that could interfere like drinking alcohol and eating red meat.

Results of the coffee study

Without normalizing for the factors mentioned above the study results were as follows. Study participants had less than a cup of coffee and three cups a day had a 5% to 9% lower risk of dying than those who drank no coffee. Those who drank more than three cups a day did not see any benefit.

However, when the researchers removed all the confounding factors and compared the various groups again, the following emerged:

  • Less than 1 cup of coffee per day: 6% lower death rates than non-coffee drinkers.
  • 1 cup to 3 cups of coffee per day: 8% lower death rates.
  • 3 to 5 cups of coffee per day: 15% lower death rates.
  • More than 5 cups of coffee per day: 12% lower death rates.

Both caffeinated and decaffeinated coffee reducing mortality rates

Ming Ding was associated with another research paper that had shown that coffee drinkers have a lower risk of developing type 2 diabetes and heart disease. She found that both caffeinated and decaffeinated coffee reduced the risk of getting diabetes later.

When asked about what would be responsible for the reduced death rates with coffee consumption, Ding explained. “There are at least two known chemicals in coffee, namely lignans and chlorogenic acid. They both could reduce inflammation and help control blood sugar. Also, both could help reduce the risk of heart disease”.

Although there seems to be a linear response up to 5 cups of coffee consumption, above 5 cups this linear relationship disappeared. The researchers could not explain whether coffee consumption reached a saturation point, whether there was yet another obscure confounding factor or whether there were detrimental effects on the adrenal glands with too much coffee consumption.

Other findings like decreased suicide rates with coffee consumption

Another finding was that it did not matter whether the coffee contained caffeine or was caffein free. The results were identical.

Many other studies did not have the large numbers to show whether or not coffee without caffeine was as effective in preventing heart disease.

Finally, there was another peculiar finding; suicide rates were down by 20% to 36%, if a person drank at least one cup of coffee per day. But if a person consumed less than 1 cup of coffee per day the suicide rate was 36% higher than the control group with no coffee consumption. This is a rather peculiar finding, particularly for the consumption of less than 1 cup of coffee. But other studies have also shown a decrease in suicide rates with coffee consumption.

No effect on liver and prostate cancer

Previous studies had shown a reduction in liver and prostate cancer. But after the removal of confounding factors this study did not show any effects on cancer causation. Cancer death rates also did not show a reduction with coffee consumption.

Discussion

The Department of Nutrition, Harvard School of Public Health in Boston, MA produced high quality nutritional studies for decades. But this study is particularly important, because it is so large giving it more statistical power; secondly, the observation time of an average of 22.5 years is longer than most coffee studies in the past. The investigators also removed the noise (called confounding factors). This helped to accomplish the objective of the study and they ended up with a very meaningful result.

Apart from saving lives by drinking coffee, diabetes and heart attack rates lower as well

The important findings were that both caffeinated and decaffeinated coffee have the same effect of saving lives. Perhaps you want to drink not more than 5 cups of coffee per day. That lowers your risk of premature death by 15%. What counts is the effect of lowering the rate of diabetes and heart attack rates. This is most likely responsible for the risk reduction. At least this was the opinion of the chief investigator. The study showed that coffee consumption did not lead to a reduction in cancer rates.

I sleep better when I drink decaffeinated coffee. So for me the notion that decaffeinated coffee had the same effect as regular coffee was important.

Coffee Could Be A Lifesaver

Coffee Could Be A Lifesaver

Conclusion

Here is a study that is large enough, went long enough, and showed decisively that coffee can reduce the death rate. Both caffeinated and decaffeinated coffee showed the effect of reducing the death rate. The mortality reduction was by 15% up to 5 cups of coffee per day. This finding was true for both males and females. Coffee seems to also reduce the suicide risk by a mechanism that has not yet been determined. Do you want to live 15% longer than your previous life expectancy would have been without coffee? Then you may now have your coffee and enjoy it!

Oct
17
2015

Depression Needs Treatment

Depression is common and depression needs treatment. 10% of all men and 20% of all women have a period of depression in their lives. In people with medical illnesses depression is more common: 20% to 40% (Ref.1).

First, the peak age for depression is usually the age of 25 to 44. There are special groups where depression is also common. In adolescents 5% are affected with depression and 13% of women tend to get depressed after delivery, a condition called postpartum depression.

Second, in any age group with depression there is a risk of suicide, but with adolescents this is particularly true.

Third, about 10% to 15% of people with general medical illness are developing depression, such as patients with Parkinson’s disease, stroke, Alzheimer’s disease, cardiac disease, HIV infection, end-stage renal failure and cancer.

Causes of depression

Officially it is not known what causes depression. That is what medical textbooks say. However, other books like Datis Kharrazian’s book “Why isn’t my brain working?” offers several scenarios that can cause depression and he has examples of cases that were cured of depression (Ref.2). He points out that deficiencies in two major brain transmitters can cause depression: serotonin and dopamine.

Serotonin

First of all, serotonin is produced in the midbrain from the amino acid tryptophan in two biochemical steps. It is important to realize that these biochemical conversions require iron, vitamin B6, vitamin B12, niacin, folic acid and magnesium as cofactors. But you also need the “large neutral amino acid transporter” (LNAA) to transport tryptophan through the blood/brain barrier into the brain.

Dopamine

Furthermore, dopamine is a neurotransmitter that is produced in the frontal lobes of the brain. Notably, it is also necessary for learning. The brain synthesizes dopamine from tyrosine, which has to be manufactured in the liver from the amino acid phenylalanine. You need to have a healthy liver to produce tyrosine, which needs to be transported through the blood/brain barrier into the brain; similar to tryptophan this requires the “large neutral amino acid transporter” (LNAA). People with hepatitis, fatty liver, insulin resistance or diabetes may have problems with the LNAA transporter, which can cause dopamine deficiency (Ref.2). But they may also have low serotonin, if tryptophan did not enter the brain because of a transportation problem. This will happen with sugar overconsumption, as insulin resistance develops and affects the LNAA transporter resulting in both low serotonin and dopamine (Ref.2).

Inflammation

Finally, in the 1990’s researchers confirmed that inflammation is also a possible factor in the causation of neurological disease including depression. Ref. 2 points out that gut issues can become brain issues as inflammatory substances can leak trough a leaky gut into the blood stream and trough a leaky blood/brain barrier into the brain. Hypothyroidism can activate brain inflammation and lead to an imbalance of the neurotransmitters. Gluten sensitivity is also an important cause of depression through the inflammatory connection, but few physicians recognize the full impact of this.

Tests for depression

There are no laboratory tests that would define depression. However, every patient should receive a blood test to check for hypothyroidism, a common cause of depression. When the tests confirm hypothyroidism, the physician can easily treat this with thyroid hormone replacement.

Otherwise the physician diagnoses depression by doing a mental status examination, history and review of symptoms. A good start is to ask: “In the past 2 weeks how little interest or pleasure in doing things have you had?” and “Have you been feeling down, depressed, or hopeless in the past 2 weeks?” (Ref.3).

There are detailed psychometric questionnaires available such as the Beck Depression Inventory that can assist the physician to establish the diagnosis.

Myths of depression

One of the myths regarding depression is that it would be contagious. As a matter fo fact, a study on 2000 high school students showed that depression was not infective. The contrary was true: human interaction with friends who had a “healthy mood” improved depression. By the same token, when you constantly compare yourself with your Facebook friends, and you are not in the best mood, your mood may worsen and you could become depressed.

Treatment of depression

Despite advances in the treatment of depression the response rate with antidepressant therapy has a limit of 60% to 70%. According to Ref.4 inadequate dosing and misdiagnoses account for the fact that 30% to 40% of treated people with depression have treatment failures. Typically the first antidepressant involves a selective serotonin reuptake inhibitor (SSRI), but newer trials have shown that the older monoamine oxidase inhibitors (MAOIs) have a higher success rate when treating depression initially (Ref.4).

For example, a good antidepressant for mild to moderate depression is St. John’s wort, which is recommended by Ref. 5 as having less side-effects as other antidepressants.

In treating resistant depression the psychiatrist often employs other combinations of antidepressants. In addition the health professional recommends to add cognitive/behavioral therapy, which makes the overall treatment more successful. It goes without saying that complicated cases of depression belong into the hands of an experienced psychiatrist.

Suicides

Unfortunately a mental disease like depression still has a stigma attached to it. As a result many people are in deep denial about the fact that mental disease exists. Friends who do not understand depression may inadvertently say things that make the symptoms of the depressed person more severe and distance themselves at a time when they would need support from friends. The end result is that the patient feels lonely, misunderstood and that suicidal thoughts enter the mind. Men often resist seeking treatment for depression, women are better in seeking professional help and getting effective treatment.

Need for a psychiatrist to help prevent suicides

This is where a psychiatrist needs to intervene. If this does not happen, people start attempting suicide and finally commit suicide. In the US committed suicides have a gender ratio of male to female of 3:1 to 10:1. These situations become very difficult. The family needs to step in and talk to the patient. It is best to accompany the patient to the hospital for an assessment. You may want to go to the hospital in your private car or by ambulance. Don’t be shy to call 911 for an ambulance. Better to be cautious than have a major crisis that ends in completed suicide.

Alternative depression treatments

There are alternative treatments for depression.

  1. Magnetic therapy for depression: This therapy is also called transcranial magnetic stimulation (TMS) and was approved for Canada and in 2008 by the FDA. But it is not as powerful according to Ref. 3 as unitemporal electroconvulsive therapy.
  1. Bifrontal electroconvulsive therapy (ECT): Electroconvulsive therapy with two pedals applied to the front of the skull appears to have the best results in terms of treating depression.
  2. Omega-3 fatty acids (EPA and DHA) are powerful anti-inflammatory agents, which will take care of the inflammatory component of depression. Both fish oil and krill oil in combination give the optimal response as outlined here.

Vitamin D3 and light box therapy

  1. Vitamin D3 is also anti-inflammatory and will contribute to an improvement with existing depression, but it also helps prevent the development of depression when taken in regularly as a supplement.
  2. Light box therapy: The observation of seasonal affective disorder (SADS) can develop as a result of lack of light. This has led to the discovery that light boxes are helpful for treating depression and also for prevention of depression due to seasonal affective disorder.

The patients should use a light box for 30 minutes every morning during the fall and winter months. The box should emit at least 10,000 lux. Improvement can occur within 2 to 4 days of starting light therapy, but often it takes up to 4 weeks to reach its full benefit.

Avoid alcohol and too much sugar

  1. It is known for a long time that alcohol is a depressant; it can actually cause depression and in persons with bipolar disease it can trigger a flare-up of that disorder as well.
  2. Finally it matters what you eat: sugar and too much starchy foods (high glycemic index carbs) lead to insulin overproduction and insulin resistance. This causes inflammation, and this will cause depression. As mentioned earlier it also lowers the two key brain transmitters, dopamine and serotonin.

The solution is an anti-inflammatory diet, the Mediterranean diet without sugar and high glycemic index carbs; only low glycemic index carbs are part of this diet. This will normalize insulin production and eliminates inflammation.

B vitamins, electroacupuncture and exercise

  1. Vitamin supplements: Folate and vitamin B12: Up to 1/3 of depressed people have folate deficiency. Supplementation with 400 mcg to 1 mg of folic acid often helps. Vitamin B12 should also be taken to not mask a B12 deficiency (Ref.5). Folate and vitamin B12 are methyl donors for several brain neuropeptides.
  2. The symptoms of depression often improve with electro acupuncture, as shown in many studies. This treatment ameliorates the symptoms of depression and seems to work through the release of neurotransmitters in the brain (Ref.6).
  3. Exercise on a regular basis helps to equalize the mood and seems to exert a slight anti-depressant effect on the person who engages in regular physical activity.
Depression Needs Treatment

Depression Needs Treatment

Conclusion

I have attempted to show the complexity of depression and what we know about its causes and treatment. Very likely there are several causes for depression and further research will hopefully bring more clarity to this. Over the years psychiatrists have developed treatment modalities, both conventional and unconventional, by trial and error. The physician and patient need to use common sense: if a treatment is working, stick to it and use it. If it does not work, move on and try something else. More complex cases should be referred to a psychiatrist who has the most experience with patients that are difficult to treat. Do not neglect life-style factors and alternative depression treatments as they can often help to stabilize depression significantly. We all must be vigilant about suicide risks in depressed patients and act by calling 911, if necessary to intervene.

More info on depression: http://nethealthbook.com/mental-illness-mental-disorders/mood-disorders/depression/

References

1. Depression, Major: Fred F. Ferri M.D., F.A.C.P., Ferri’s Clinical Advisor 2016, by Elsevier, Inc.

2. Dr. Datis Kharrazian: “Why Isn’t My Brain Working?” © 2013, Elephant Press, Carlsbad, CA 92011

3. Goldman-Cecil Medicine “Major depressive disorder” 2016, by Saunders, an imprint of Elsevier Inc.

4. Massachusetts General Hospital Comprehensive Clinical Psychiatry, Second Edition: Theodore A. Stern MD, Maurizio Fava MD, Timothy E. Wilens MD and Jerrold F. Rosenbaum MD © 2016, Elsevier Inc.

5. Rakel: Integrative Medicine, 3rd ed. © 2012 Saunders.

6. George A. Ulett, M.D., Ph.D. and SongPing Han, B.M., Ph.D.: “The Biology of Acupuncture”, copyright 2002, Warren H. Green Inc., Saint Louis, Missouri, 63132 USA

Sep
19
2015

Obesity Shortens Life

This article is about the fact that obesity shortens life. Of all the factors that definitely shorten life, obesity stands out like a giant. Let’s review a couple of facts regarding obesity:

  1. Americans who were born between 1966 and 1985 became obese at a much earlier age than their parents
  2. Obesity occurs at a younger age than in the past. 20% of people born between 1966 and 1985 were obese in their 20s.
  3. The longer you are obese, the higher the chance of getting seriously sick or dying prematurely from complications of associated diseases like diabetes, heart attacks, strokes, kidney disease, liver disease and cancer.
  4. Severely obese people live up to 20 years less than non-overweight people.
  5. Obesity causes about 300,000 deaths in the U.S. annually

Change of metabolism

Obesity shortens life. Obesity leads to a change in metabolism, which is known as metabolic syndrome. The liver changes its metabolism slightly producing more triglycerides, LDL cholesterol and clotting factors, which increases the risk for heart attacks, strokes and pulmonary emboli. The pancreas produces more insulin, which gives rise to reactive hypoglycemia. This means that 2-3 hours after a meal you become hungry as your blood sugar declines from the extra insulin. You are craving a sugary drink, a donut or other starchy food (pizza, fries, bread etc.). Unfortunately, these types of foods reinforce the metabolic syndrome: the liver changes the sugar into LDL cholesterol and triglycerides.

Excess sugar oxidizes LDL cholesterol

Excess sugar will oxidize the LDL cholesterol, which causes atheromas (hardening of the arteries). Protein is being caramelized, which is called “advanced glycation end-products” or AGEs. This reference clearly explains how to counter this: increase your consumption of fish, legumes, vegetables, fruits, low-fat milk products and whole grains; also reduce your intake of solid fats, full-fat dairy products, fatty meats, and highly processed foods. There are other hormone changes that take place in obese people.

Death statistics due to obesity

In this study 849 autopsies were performed over 10 years, of which 32.3% were of obese persons. Leading causes of deaths in obese people were: malignancy (31.4%), infection (25.9%), ischemic heart disease (12.8%), pulmonary embolism (6.2%) and liver disease (2.9%). Table 2 of this link shows the causes of death in non-obese individuals as well: malignancy (32.5%), infection (23.8%), ischemic heart disease (10.4%), pulmonary embolism (2.9%) and liver disease (0.7%). The figures do not look all that different except that liver disease and pulmonary embolism are significantly more often the cause of death in obese patients than in normal weight patients. What you do not see in these figures is that obese people get these conditions at a much younger age as a result of complications from the associated diseases like diabetes, high blood pressure, cardiovascular disease, osteoarthritis, kidney disease and liver disease.

Diabetes

The metabolic changes with regard to the metabolic syndrome include insulin resistance.

As obesity worsens the balance is lost where the body can compensate and type 2 diabetes develops with increased blood sugar values and symptoms of diabetes. Surprisingly with regular exercise and changes in food intake (adopting a low glycemic index diet) this can be treated successfully. Usually this change is also associated with some weight loss, which helps to stabilize the metabolism. If nothing is done to to change diabetes, there is a high risk for heart attacks, strokes and subsequent secondary conditions like diabetic nephropathy, retinopathy, diabetic neuropathy and vascular complications.

Uncontrolled high blood pressure

High blood pressure is part of the metabolic syndrome. Unfortunately in obesity it is often difficult to control and may require several different antihypertensive medications in combination to control it. One way to quickly get the blood pressure under control is to make a concentrated effort to reduce a few pounds of weight; this can be achieved by cutting out refined carbs and sugar and starting an exercise program of walking and swimming.

Smoking

Smoking continues to remain a problem. Men as a group are now smoking less while women are increasing their smoking rates. Smoking causes various cancers, but also increases death rates from heart disease and strokes. In connection with obesity it is clear that the obese smoker has the highest risk of dying prematurely. This is depicted in this link based on the original Framingham study.

Disabilities and nursing homes

Obese people get disabled earlier, ending up in nursing homes. This poses a huge problem there for the staff. Back injuries and disabilities in the caregivers of nursing homes have increased significantly in the last few decades.

Osteoarthritis

80% of hip replacements and 90% of knee replacements are due to osteoarthritis. Obesity is the strongest modifiable risk factor that leads to osteoarthritis and subsequent surgery. There is a lot of morbidity and mortality associated with total knee and total hip surgeries. Part of this is the susceptibility to clot formation from the changes in metabolism associated with the metabolic syndrome. This often leads to pulmonary emboli and higher death rates following surgery when compared to surgery in people with normal weight.

Heart attacks and strokes

As there is an increase of the amount of heart attacks and strokes in overweight and obese people it is important to reduce your BMI when you realize that it is creeping up. Regular exercise along with a Mediterranean diet helps to improve this. Avoid processed foods that often have hidden sugar and refined carbs in them. Also cut out sugar. Use stevia, a natural sweetener, if you want to sweeten your food or drinks.

Nonalcoholic fatty liver disease (NAFLD)

In the past nonalcoholic fatty liver disease was rare. Now with the increase of obesity it is common. It can lead to liver cirrhosis with hepatic failure, a common cause of death. But after several years of liver cirrhosis, liver cancer may develop within the cirrhotic liver. Physicians saw this condition only rarely in decades past.

Obesity shortens life: Kidney disease

With obesity there is a negative effect on the kidneys from the metabolic syndrome. Hyperinsulinism affects the capillaries of the filtration units, called glomeruli. They start to proliferate and undergo a form of degenerative change, called glomerulosclerosis. This decreases the filtration capacity of the glomeruli and the kidneys as a whole. After a few decades of this process kidney failure can set in. When an obese person develops diabetes, this will also have a negative effect on kidney function and accelerate the deterioration of kidney function. The end result is kidney failure, which requires dialysis or a kidney transplant.

Cancer and obesity

Obesity shortens life. Chronic inflammation that is worsened by the metabolic syndrome leads to higher rates of various cancers. A prospective study of more than 900,000 US adults was conducted for 16 years. In 1982 when the study was started none of the participants had cancer. After 16 years 57,145 of the study participants had died of cancer. Those in this study who had a BMI of 40.0 or more had cancer death rates that were 52% higher for males and 62% higher for females when compared to normal weight men and women.

Higher cancer rates in people with obesity

It was noticeable that the digestive tract showed higher cancer rates in the obese: esophagus, liver, gallbladder, pancreas, colon and rectum; other more frequent cancers were kidney cancer, multiple myeloma and non-Hodgkin’s lymphoma. There were also trends of higher cancer death rates with regard to cancer of the stomach and prostate in men and breast cancer, uterine cancer, ovarian and cervical cancer in women. The authors concluded that due to the rising obesity rates in the US population cancer rates in men will soon reach the 14% level and in women the 20% level out of the total death rates.

Treating obesity

Treatment of obesity requires a multifaceted approach. I have discussed this in detail in this blog. Briefly, the diet of the obese person needs to be closely looked at. Sugar and starchy foods need to be eliminated. Low glycemic foods like vegetables, lean meat and salads should be encouraged. A regular exercise program needs to be instituted, starting with swimming and walking. Later a gradual transition into gym type activities could be contemplated.

Weight loss surgery has been successfully applied in some obese patients with a BMI that is greater than 30.0 up to a BMI of 39.9. In a 5-year follow up after LAP-band surgery no surgical complications were reported and the mean percentage weight loss was 15.9±12.4%.

Obesity Shortens Life

Obesity Shortens Life

Conclusion

Obesity shortens life. Obesity is a condition that has been gradually developing since the 1980’s. When you look at the food intake changes rationally it is not surprising that this is happening. Sugar consumption, high-fructose corn syrup consumption and the consumption of processed food have to be cut down, if not cut out completely. You can forget shopping at the middle section of any grocery store, where all that processed food is located. Go to the vegetable section and buy a lot of food from there. Low fat dairy products, eggs, and low-fat meats as well as salmon and other seafood are foods that are healthy. There is one problem though and that is the feeding of antibiotics to chickens, turkeys and beef cattle. This leads to superbugs and changes your gut flora.

Eat organic foods

I suggest you buy organic meats. I eat organic food and have cut out wheat also as wheat underwent forced hybridization in the 1970’s. All of the wheat in the world now is this type of wheat that is too rich in gliadin, which causes leaky gut syndrome and autoimmune diseases. For this reason, I avoid all wheat.

Gradually shed your pounds

I see no reason why obese people could not gradually shed their pounds and regain their stable metabolism. Those with diabetes will be able to shed that diagnosis as they shed their pounds. The kidney and liver function will also stabilize when you shed enough pounds. The goal should first be to reach a BMI of 25.0 to 30.0, which is the overweight category. The next goal would be to aim for shedding even more pounds until you reach a BMI of fewer than 25.0. If you say this is too tough to do, I am saying: giving up is not an option. Cherish your health!

Incoming search terms:

Aug
29
2015

Problems With The Western Diet

Lately there have been various news reports cautioning us about the Western diet. We eat too much processed food, we eat too much sugar and we have to be careful with how much fat and what kind of fat we eat. Take this story from the CNN. Half the world lives in big cities. And this number will reach 70% in the year 2050, if the urbanization trend continues at the same rate. With it comes the consumption of fast food. The wealthier people are, the more meat they eat. This is exactly what is bad for us. Too much meat can cause gout, particularly when paired with alcohol. First it is time to explain some more about the Western diet. “The biggest features of a Western diet are overconsumption of over-refined sugars, highly refined and saturated fats, animal protein and a reduced intake of plant-based fibers,” says Ian Myles. He is located at the U.S. National Institute of Allergy and Infectious Diseases. This statement is specific enough: we are eating too much fat, red meat, salt and sugar, and too little fiber.

Too much fat

In processed foods we get too many omega-6 fatty acids, which have been shown to cause clogging of arteries and causing heart attacks and strokes, if not balanced with enough omega-3 fatty acids. But many processed foods still have hidden trans fats, which distribute free radicals in your system; this in turn causes hardening of the arteries again. Free radicals also age you faster. A candy bar with palmitic acid and fructose for instance, leads to a slow grade inflammation. The immune system mistakenly takes palmitic acid for the gut bacterium E.coli and mounts an immune reaction. This low-grade inflammation causes inflammation in the blood vessels, but also weakens the immune system. The sugar part of the candy bar oxidizes LDL cholesterol leading to clogging of arteries, which causes heart attacks and strokes.

Too much red meat

Grain fed and antibiotic treated regular beef changes the gut bacteria and can cause super bugs. The change of the gut flora can lead to inflammation in the gut lining and something called “leaky gut syndrome”. We carry almost 2 pounds of gut bacteria in us at any given time. But residual antibiotics from regular beef and chicken reduces that amount and changes the composition of our gut flora.

You can read in this blog that the changes taking place from consuming regular beef changes your liver metabolism and leads to accelerated hardening of the arteries, which in turn causes deadly heart attacks and strokes. On the other hand, grass fed beef or organic beef do not do this. To prevent leaky gut syndrome, heart attacks and strokes from developing you can take probiotics every day, which should include these two species: Lactobacillus acidophilus and Bifidobacterium bifidus. This keeps your gut flora stable and does not allow your food to undermine your health.

To much salt and sugar

Too much salt is often in processed food to prolong the shelf life. But we humans are very sensitive to overdoses of salt. Our kidneys have to work overtime to get rid of the excess salt. We need to drink enough water to allow the kidneys to produce urine, which will eliminate the excess salt. Persistent excessive salt intake will also cause high blood pressure. High blood pressure can cause heart problems, strokes and aortic aneurysms. Restaurant food often contains too much salt and sugar.

Too little fiber

The more food is processed, the less fiber it will contain. If you go for the pizza, it may taste good, but where is the fiber? If you eat bread and butter, where is the fiber? You may say that you like a donut. I ask you again: where is the fiber? The end result is that toxins that normally would have been bound to fiber in the colon and were eliminated in the stool are now interacting with the wall of the colon causing colonic polyps and colon cancer. It may not only be fiber as plant-based diets rich in fruits, non-starchy vegetables, legumes, and whole grains were shown to be associated with a lower risk of the most common cancers. That’s the reason why people who consume a Western diet have higher rates of cancer in general. They lack fruits and vegetables.

Polyunsaturated fatty acids

The recommendation in the 1980’s until about 2010 of a low fat diet to prevent heart attacks and strokes has failed miserably. It turned out that polyunsaturated fatty acids are of the omega-6 type, which gets metabolized into arachidonic acid and causes inflammation. The immune system gets suppressed from the chronic inflammation and the person becomes more prone to infections. As low fat diets are typically high in carbohydrates, there is a calorie surplus causing weight gain. Dr. Fife explains in his book that polyunsaturated acids interfere with the insulin receptor feeding into insulin resistance, which makes it even more difficult to control the metabolism and leads to more weight gain (Ref.1). The end result is what we have observed over the last few decades, a relentless obesity wave in the civilized world. It is a direct result of the Western diet.

Cancer caused by the Western diet

Breast cancer, colon cancer and prostate cancer are cancers that are related to the Western diet. But there are likely many other cancers that are also caused by it.

We know that free radicals cause cancer, such as from trans fats and rancid polyunsaturated fatty acids found in processed foods. Cancer is more common in obese people and people with diabetes.

Habits that make us eat more

There are habits that make us eat more like snacking and falling for so-called “fitness food” which contains dubious ingredients. It may come as a surprise, but married people can also fall prey to unhealthy habits together, forgetting about working out and sneaking in “skinny cocktails”. Read what Cynthia Sass, registered dietician had to say about this on CNN.

Solution to the Western diet

You may expect me to say that you should modify this or that in the Western diet. Modification does not work. You have to get radical here! The real solution is to abandon the Western diet altogether. Replace it with the Mediterranean diet without sugar and starchy foods. It is not that as bad as you can see from 1 week of recipes that my wife included in my book: “A survivor’s Guide To Successful Aging”.

You can eat cooked organic spinach, a piece of meat with slices of Avocado for breakfast. Cooking is done mostly with coconut oil or olive oil. Alternatively you may enjoy an egg or egg white vegetable omelette with lots of greens, mushrooms, onions and salsa and avocado on the side. Add to this caffeinated or decaffeinated coffee with stevia. Alternatively, a bowl of rolled oats, flaxseed and nuts with fresh fruit and organic milk, goat milk or yoghurt would make an excellent, sustaining breakfast. I am mentioning all of this to show you that you can get away from your familiar pancakes with maple syrup, sausages, waffles, toasts and muffins etc.

Food needs to be prepared form scratch with organic ingredients. GMO foods need to be avoided as the final judgment on these is decades away, and you do not want to become a human guinea pig.

Problems With The Western Diet

Problems With The Western Diet

Conclusion

The only way to “improve” a Western diet is to eliminate it and replace it by the Mediterranean diet. Throw all the processed food into the trash where it belongs! Avoid omega-6 fatty acids (polyunsaturated fatty acids), which have been shown to weaken the immune system and cause insulin resistance. The best fats are omega-3-fatty acids from marine oils (fish oil), coconut oil and olive oil. Forget all the other oils that are heavily advertised. They are not healthy.

I stick to organic foods although they are more expensive. Don’t forget that apart from a good diet you need to engage in a regular exercise program in order to prevent heart disease and cancer. And don’t stress out over the changes that you are about to make. Remember to manage your stress and relax!

References:

  1. Bruce Fife, C.N., N.D.: “The Coconut Oil Miracle”, 5th edition,2013, Penguin Books, NY 10014

Incoming search terms: